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Adrenal Anatomy
Adrenal Anatomy
The adrenal cortex arises fro m the coelomic mesoderm between the fourth and sixth weeks of gestation.
Adrenal Anatomy
The adrenal medulla is derived from cells of the neural crest that also form the sympathetic nervous system and the sympathetic ganglia.Some of these neural crest cells migrate into the adrenal cortex to form the adrenal medulla, but chromaffin tissue may also develop in extraadrenal sites. The most common site of extraadrenal chromaffin tissue is the organ of Zuckerkandl, located adjacent to the aorta near IMA.
Adrenal Anatomy
The glands weigh about 4g each, located in the retroperitoneum along the superior-medial aspect of the kidneys. Yellow appearance because of their high lipid content. 3-5 cm in length, 4-6mm in thickness
Adrenal Anatomy
Left>right Receive arterial blood from branches of the inferior phrenic artery, aorta, and renal arteries. The right adrenal vein is short and exits the gland medially to enter the vena cava. The left adrenal vein exits anteriorly and usually drains into the left renal vein. As a result, adrenal venous catheterization is accomplished more easily on the left than the right.
Adrenal Anatomy
The adrenal cortex is composed of three zones histologically. Outer zona glomerulosa, site for aldosterone synthesis. Central zona fasciculata and inner zona reticularis produce both cortisol and androgens.
Adrenal Anatomy
Most of the blood supply to the medulla comes from venous blood draining through the cortex. This provides the adrenal chromaffin cells with high concentration of the enzyme phenyethanolamine Nmethyltransferase (PNMT) required for conversion of norepinephrine to epinephrine.
The Cortex
The Cortex
Zona glomerulosa is the exclusive site of production of aldosterone because it lacks the enzyme 17 alpha hydroxylase necessary for production of 17 a- progesterone and 17 apregnalone, which are the precursors to cortisol and androgens.
The Cortex
Zona fasciculata and reticularis function as a unit to produce cortisol, androgens, and small amounts of estrogen, but it lacks the enzymes necessary to convert 18hydroxycorticosterone to aldosterone.
Cortex
Cholesterol is the precursor from which all adrenal steroids are synthesized. Conversion of cholesterol to pregnenolone is the rate limiting step in adrenal steroidogenesis and is the major site of action of ACTH.
Steroidogenesis
Cholesterol
Cholesterol desmolase
17-hydroxylase
17,20 lyase
Pregnenolone
17-Hydroxypregnenolone
3 hydroxysteroid dehydrogenase
DHEA
Progesterone
17-Hydroxyprogesterone
21-hydroxylase
Androstenedione
11-Deoxycorticosterone
11-Deoxycortisol
Testosterone
11-hydroxylase
Corticosterone
Aldosterone synthase
Cortisol
Estradiol
Aldosterone
Glucocorticoids
Glucocorticoids
Cortisol, like ACTH is secreted in a pulsitile manner, and plasma levels closely parallel those of ACTH. Superimposed on this is a circadian rhythm that results in peak cortisol levels in the early morning and a nadir in the late evening. Physical and emotional stress (trauma, surgery, and hypoglycemia) increase cortisol secretion by stimulating release of CRH and ACTH from hypothalamus and pituitary respectively.
Glucocorticoids
Normal daily production of cortisol is 10-30mg. The liver is the main site of metabolism. Two major metabolites are 17hydroxycorticosteroids and 17ketosteroids, excreted in the urine.
Glucocorticoids
Metabolic effects are stimulation of hepatic gluconeogenesis, inhibition of protein synthesis, increased protein catabolism, and lipolysis of adipose tissue.
Glucocorticoids
The increased release of AA from muscle protein and release of glycerol and free fatty acids from fat provide the substrate for hepatic gluconeogenesis. Also increase glycogen synthesis, peripheral uptake of glucose is inhibited, and may cause hyperglycemia and increased insulin secretion.
Glucocorticoids
Loss of collagen, impair wound healing by inhibition of fibroblasts. Inhibit bone formation, reduce calcium absorption by gut (steroid induced osteoporosis).
Glucocorticoids
Numerous antiinflammatory actions, which include inhibition of leukocyte mobilization and function, decreased migration of inflammatory cells to sites of injury, decreased production of inflammatory mediators (IL-1, leukotrienes, and bradykinins). Also essential for cardiovascular stability, as evidenced by the collapse that occurs in patients with adrenal insufficiency.
Androgens
Dehydro-3-epiandrosterone (DHEA) and DHEA sulfate. Minimal direct biologic activity. In periphery they undergo conversion to androgens, testosterone, and dihydrotestosterone.
Androgens
Increased in Cushing syndrome, adrenal carcinoma, congenital adrenal hyperplasia. In adult men accounts for only 5% of testosterone, in prepubertal boys, however, increased production may be manifested by the early development of secondary sexual characteristics and penile enlargement. In females, manifested by acne, hirsuitism, virilization, and amenorrhea.
Aldosterone
Maintains extracellular fluid volume and regulation of sodium and potassium. Renin-angiotensin system regulates it.
Aldosterone
Renin is secreted by juxtaglomerular cells of the kidney in response to decreased pressure in the renal afferent arterioles. Decreased sodium concentration sensed by the macula densa promote renin as well.
Aldosterone
Renin is also stimulated by hyperkalemia, and inhibited by potassium depletion. Angiotensin II is a potent vasoconstrictor, also stimulates zona glomerulosa to secrete aldosterone. Aldosterone then stimulates reabsorption of sodium in exchange for potassium and hydrogen ion secretion.
Renin-Angiotensin
Cushings Syndrome
Constellation of signs and symptoms that result from chronic glucocorticoid excess. Most common source is iatrogenic administration of glucocorticoids. ACTH-secreting tumors of pituitary are the most common cause of spontaneous Cushing syndrome.
Exogenous
Pituitary adenoma
(Cushings Disease) Ectopic ACTH production Ectopic CRH production Adrenal adenoma
Adrenal carcinoma Adrenal hyperplasia
Cushings Syndrome
Pituitary Cushing, also termed Cushing disease, accounts for 70% of all cases of Cushing syndrome. Ectopic ACTH secreting tumors comprise 15% of all cases and associated with small cell cancers of the lung. Primary adrenal tumors (adenomas, carcinomas) account for 15-20% of cases.
Cushing Syndrome
These patients lose diurnal variation in cortisol levels. Elevated levels of urinary free cortisol present in 90% of patients. Normally only 1% of cortisol excreted in urine. Low dose dexamethasone suppression test will suppress pituitary secretion of ACTH and adrenal production of steroids. So, if am plasma cortisol is suppressed then Cushing is ruled out.
Cushing Syndrome
Plasma ACTH levels are used to differentiate ACTH-dependent (pituitary and ectopic ACTH secreting tumors) from adrenal causes of Cushing syndrome. With primary adrenal tumors, ACTH should be suppressed (<5pg/ml). With pituitary causes, it will be normal or slightly elevated (15-200pg/ml). With ectopic ACTH secreting tumors, it will be markedly elevated.
Cushing Syndrome
High Dose Dexamethasone Test may be used to distinguish pituitary from non-pituitary causes of ACTHdependent Cushing syndrome. Rationale is that the high dose will not suppress cortisol production from a primary adrenal neoplasm or ectopic ACTH secreting tumor.
Cushings Syndrome
Cushings Syndrome
Cushings Syndrome
Late-afternoon/midnight measurement of plasma cortisol + ACTH
No Cushings
ACTH-dependant Cushings Syndrome
High dose dexamethasone suppression test ? Metyrapone stim. Test, ?inferior petrosal Sinus sampling
Adrenal CT/MRI
Ectopic ACTH
Surgical removal
cure Failure Pituitary irradiation or Bilateral adrenalectomy
Weight loss, anorexia Nausea, vomiting Weakness, tiredness, fatigue GI complaints abdominal pain Diarrhea Muscle pain Salt craving Hypotension, dizziness, syncope Lethargy, disorientation
90% 66% 94% 61% 28% 18% 16% 14% 14% 12%
Autoimmune Steroid withdrawal Adrenal atrophy (lymphocytic adenitis with fibrosis) Malignant infiltration Hemorrhage Sepsis Iatrogenic (post op) Sarcoidosis, Tuberculosis
Hyponatremia Hyperkalemia Azotemia Hypercalcemia 10-30% associated with other endocrine disorders AM cortisol level, ACTH level Rapid ACTH test
0.25 mg IV cosyntropin Measure cortisol before and 60 min after Cortisol level should be >18mcg/dl at 60 min
Acute stress dose dexamethasone Chronic hydrocortisone (200-300mg) plus fludrocortisone (.05-1.0mg/day) ACTH stim test to establish diagnosis
Hyperaldosteronism
1. 2. 3. 1. 2.
Primary (suppressed renin) Adrenal adenoma Adrenal carcinoma Bilateral hyperplasia Secondary Renal artery stenosis Edematous states (cirrhosis, renal failure)
Hyperaldosteronism, Diagnosis
CT scan Adrenal vein sampling Urinary 18-hydroxycortisol elevated in adenoma. plasma hydroxycorticosterone (overnight recumbent)- > 100 in adenoma
Hyperaldosteronism, Diagnosis
Serum K < 3.6 mEq/L Plasma renin activity (PRA) < 1 ng/ml Plasma aldosterone >22 ng/dL Urine aldosterone > 14 mcg/24hrs Urine K > 40 mEq/24 hrs Plasma aldosterone:PRA ratio > 50:1
Hyperaldosteronism, Treatment
Adrenal Medulla
L-Tyrosine converted to L-DOPA converted to Dopamine converted to L-Norepinephine converted to L-Epinephrine Degrades to VMA, metanephrine, normetanephrine
Catecholamines
Exert their effect by interaction will cellspecific receptors. The principle physiologic effect of alpha receptor stimulation is vasoconstriction.
Catecholamines
Two types of Beta receptors exist. Beta-1 receptors mediate inotropic and chronotropic stimulation of cardiac muscle, whereas Beta-2 receptors induce relaxation of smooth muscle in non-cardiac tissues, including blood vessels, the bronchi, uterus, and adipose tissue.
Pheochromocytoma
10% extraadrenal 10% bilateral 10%familial 10%children 10% malignant 10% assoc with MEN 10% present with a stroke
Pheochromocytoma
Pounding in chest (from B-1 receptor mediated increase in CO). Headaches Hands and feet become moist, cool, and pale (from A-receptor induced peripheral constriction). 10% present in pheocrisis 50% found as incidentaloma.
Pheochromocytoma
Elevated BP, fever, flushing, sweating, anxiety, feeling of doom. Most attacks are short-lived (15min). May be precipitated by position, stress, physical activity.
Pheochromocytoma, Diagnosis
24hr urinary catecholamines (NE, Epi, Dop) and metabolites (metanephrine, normetanephrine, VMA). Plasma catecholamine or metabolites during episode. Elevated serum epinephrine suggests pheo in medulla or Organ of Zukerkandl NO FNA! (can precipitate hypertensive crisis).
Pheochromocytoma, Diagnosis
Thin cut CT detects most lesions: 97% intraabdominal. MRI: 90% pheos bright on T2 weighted scan MIBG: used for extraadrenal, recurrent, multifocal, malignant disease. Local invasion, disease outside of adrenal/paraganglionic tissue. No histological or clinical criteria can differentiate malignant disease.
Malignant disease
Pheochromocytoma, Treatment
Treat HTN Expand intravascular volume Control cardiac arrhythmias most commonly given 1-3 wks prior to OR. Other -adrenergic antagonists, CCB, ACEI used
Pheochromocytoma, Treatment
PO salt and fluid repletion. May need -blocker as antiarrhythmic. Do not start until after pt -blocked. Metyrosine decreases catecholamine synthesis.
Incidentaloma
70-94% are benign and nonfunctional >3cm more likely to be functional Up to 20% may be subclinically active Increase with age, no change in sex 5-25% will increase in size by at least 1cm
Incidentaloma
Increased risk of adrenocortical carcinoma with increasing size <4cm 2% 4.1-6cm 6% >6cm 25% No change with age or sex
Incidentaloma, Workup
Bioclinical examination
Dexamethasone suppression test Urinary/plasma catecholamine/metanephrines Serum potassium, plasma aldosterone concentration-plasma renin activity ratio (if hypertensive) Stool for occult blood CXR Mammogram
Unilateral, functioning tumors. >6cm; 4-6 cm is a grey area. Rapid growth rate. Imaging not c/w benign adenoma. No surgery if workup reveals metastasis. ?Younger patients (increased lifetime cancer risk, longer f/u, lower incidence of adrenal masses).
<4cm, nonfunctioning tumors. CT in 3 and 12 months. If no increase in size, no data to support further imaging. ? Periodic hormonal testing. If a tumor will start to hyperfunction, this will most likely happen in 3-4 yrs.
Functioning mass
Nonfunctioning mass
adrenalectomy
Consider FNA
adrenalectomy
+ FNA
- FNA
observe Adapted from Camerons, Current Surgical Therapy 7th ed. Pg 635 adrenalectomy